E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Motor neuron disease characterized by atrophy and muscle weakness in the spinal and bulbar region |
Malattia motoneuronale caratterizzata da atrofia e debolezza muscolare nel distretto spinale e bulbare |
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E.1.1.1 | Medical condition in easily understood language |
SBMA is an adult motor neuron disease that leads to muscle atrophy and weakness in the spinal and bulbar region. |
La SBMA è una malattia motoneuronale dell'età adulta che conduce a atrofia e debolezza muscolare nel distretto spinale e bulbare. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10068597 |
E.1.2 | Term | Bulbospinal muscular atrophy congenital |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the effect of Beta2-agonist stimulation on muscle as a therapeutic strategy for SBMA |
Valutare l’effetto della stimolazione beta2-agonista sul muscolo come strategia terapeutica per la SBMA |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives include the assessment of the persistence of the effect (if any) after prolonged treatment and the tolerability of the treatment in terms of adverse effects emerging from the treatment |
Gli obiettivi secondari comprendono la valutazione della persistenza dell’effetto (se esiste) dopo il trattamento prolungato e la tollerabilità del trattamento in termini di effetti avversi emergenti dal trattamento |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For inclusion in the study, subjects must fulfill ALL of the following criteria: 1) males who have received a genetically confirmed diagnosis of SBMA (AR CAG repeat number > 38); 2) aged between 18 and 75 (+364 days) years; 3) displaying one or more of the following clinical symptoms: muscle atrophy, limb weakness, bulbar palsy; 4) able to walk independently with or without a cane or other supporting device (all supporting devices are acceptable except on wheelchair); 5) providing a written informed consent. |
Criteri di inclusione: 1) pazienti maschi che hanno ricevuto una diagnosi geneticamente confermata di SBMA (numero di ripetizione AR CAG> 38); 2) età compresa tra 18 e 75 anni (+364 giorni); 3) presenza di uno o più dei seguenti sintomi clinici: atrofia muscolare, debolezza degli arti, paralisi bulbare; 4) pazienti in grado di camminare indipendentemente con o senza bastone o altro dispositivo di supporto (tutti i dispositivi di supporto sono accettabili tranne la sedia a rotelle); 5) pazienti che forniscono un consenso informato scritto. |
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E.4 | Principal exclusion criteria |
The subject may not enter or continue in the study if ANY of the following apply at any study visit prior to randomization: 1) a documented cardiovascular disease precluding the use of beta2 agonists; 2) glaucoma, severe prostatic hypertrophy, hyperthyroidism, pheochromocytoma, and other medical conditions that, in the judgment of the investigators, would expose the patient to undue risk of harm or prevent the patient from completing the study; 3) concomitant treatment with either beta-blockers or sympathomimetic drugs; 4) inability to walk or walking only with the support of a caregiver; 5) use of beta2 agonists in the preceding 6 months; 6) participation to a interventional trial in the preceding 3 months. 7) neuromuscular disease other than SBMA |
Criteri di esclusione: 1) presenza di una malattia cardiovascolare documentata che precluda l'uso di agonisti beta2; 2) presenza di glaucoma, ipertrofia prostatica grave, ipertiroidismo, feocromocitoma e altre condizioni mediche che, a giudizio degli investigatori, esporrebbero il paziente a rischi eccessivi di danno o impediranno al paziente di completare lo studio; 3) pazienti in trattamento concomitante con beta-bloccanti o farmaci simpaticomimetici; 4) pazienti con incapacità di camminare o camminare solo con il supporto di un caregiver; 5) uso di beta2 agonisti nei precedenti 6 mesi; 6) partecipazione ad un altro trial interventistico nei 3 mesi precedenti. 7) presenza di una malattia neuromuscolare diversa dalla SBMA |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point is calculated as a 15% increase in the distance traveled in six minutes (6MWT test) at 12 months. |
L’end point primario è calcolato come un aumento del 15% nella distanza percorsa in sei minuti (test 6MWT) a 12 mesi. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1547 / 5000 Risultati della traduzione 1. mean change in 6MWT test score over 12 months of treatment (V1-V7) in the two therapeutic arms; 2. mean change in SBMA-FRS total score during 12 months of treatment (V1-V7) in the two therapeutic arms; 3. mean change in the total score on the AMAT scale during the 12 months of treatment (V1-V7) in the two therapeutic arms; 4. mean change in FVC over 12 months of treatment (V1-V7) in the two therapeutic arms; 5. mean change in the 6K total score during 12 months of treatment (V1-V7) in the two therapeutic arms; 6. mean change in serum creatinine levels over 12 months of treatment (V1-V7) in the two therapeutic arms; 7. mean change in ALSAQ-40 total score during 12 months of treatment (V1-V7) in the two therapeutic arms; 8. mean change in total score on the INQOL scale over 12 months of treatment (V1-V7) in the two therapeutic arms; 9. Percentage of patients experiencing adverse events and serious adverse events in the two therapeutic arms at V7; 10. percentage of patients experiencing side effects involving the cardiovascular system in the two therapeutic arms at V7; 11. percentage of patients with edema (identified by muscle MRI) in the two therapeutic arms at V7; 12. degree of atrophy (measured by muscle MRI) in the two therapeutic arms at V7; 13. degree of substitution of adipose fiber (measured by muscle MRI) in the two therapeutic arms at V7. |
1. variazione media del punteggio del test 6MWT durante i 12 mesi di trattamento (V1-V7) nei due bracci terapeutici; 2. variazione media del punteggio totale della scala SBMA-FRS durante i 12 mesi di trattamento (V1-V7) nei due bracci terapeutici; 3. variazione media del punteggio totale della scala AMAT durante i 12 mesi di trattamento (V1-V7) nei due bracci terapeutici; 4. variazione media della FVC durante i 12 mesi di trattamento (V1-V7) nei due bracci terapeutici; 5. variazione media del punteggio totale della scala 6K durante i 12 mesi di trattamento (V1-V7) nei due bracci terapeutici; 6. variazione media dei livelli di creatinina nel siero durante i 12 mesi di trattamento (V1-V7) nei due bracci terapeutici; 7. variazione media del punteggio totale della scala ALSAQ-40 durante i 12 mesi di trattamento (V1-V7) nei due bracci terapeutici; 8. variazione media del punteggio totale della scala INQOL durante i 12 mesi di trattamento (V1-V7) nei due bracci terapeutici; 9. percentuale di pazienti che sperimentano eventi avversi ed eventi avversi gravi nei due bracci terapeutici a V7; 10. percentuale di pazienti che sperimentano effetti collaterali che coinvolgono il sistema cardiovascolare nei due bracci terapeutici a V7; 11. percentuale di pazienti con edema (individuato dalla RM muscolare) nei due bracci terapeutici a V7; 12. grado di atrofia (misurato dalla RM muscolare) nei due bracci terapeutici a V7; 13. grado di sostituzione di fibra adiposa (misurato dalla RM muscolare) nei due bracci terapeutici a V7. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |